TMC125-TiDP35-C239 - Continued Access to Etravirine (ETR) in Treatment Experienced HIV-1 Infected Participants

• Sponsor: Janssen Sciences Ireland UC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT00980538
• Collaborator: (none)
• Enrollment: 180
• Locations: 31
• Arm: 1
• Anticipated Duration (Months): 262.7
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to provide etravirine (ETR) through this trial until participants can be switched to locally available ETR-based treatment regimens (that is, commercially available and reimbursed, or accessible through another source [example, access program or government program]), or local standard of care, as appropriate.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; HIV-1	Drug: Etravirine	Phase 3

Detailed Description

This is open label continued access trial for HIV-1 infected children/adolescents who have completed treatment in clinical (parent) trial with etravirine (ETR) sponsored by/in collaboration with Janssen Research & Development and who continue to benefit from use of ETR. At baseline visit, eligibility criteria will be checked. If eligibility criteria are met, participants will either continue on ETR dose they received in previous ETR (parent) trial or on adjusted dose if required by investigator.ETR dose adjustment will be based on weight using dosing guidelines. Assessment visits are recommended every 3 months (pediatric) and 6 months (adults). For most of participant, their next visit will be final visit with data collection. New participants entering study, will have baseline visit without data collection. Thereafter visits and assessments will be performed per local standard of care and documented in the participant's medical records only. Investigators will continue to report SAEs possibly related to ETR and pregnancies to sponsor using regular reporting. Treatment will be continued until: investigator determines that participant no longer benefits from ETR treatment (e.g based on viral load); treatment limiting toxicity; loss to follow-up; consent withdrawal; pregnancy; program termination by Sponsor; ETR-based treatment regimen becomes commercially available for participant's use, and is reimbursed, or accessed by another source (e.g access/government program) in region participant is living, or participants switched to local standard of care, as appropriate. Adult participants will receive ETR 200mg BID.Pediatric participants will receive ETR, doses as received in previous ETR(parent) trial, with weight based dose adjustment if necessary.

10 to <20kg:100mg BID (425mg or 1 tablet 100mg) 20 to <25kg:125mg BID (525mg or 1 tablet 100mg+1 tablet 25mg) 25 to <30kg:150mg BID (625mg or 1 tablet 100mg+2 tablets 25mg) >= 30kg:200mg BID (825mg or 2*100mg)

Study Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Continued Access to Etravirine (ETR) in Treatment Experienced HIV-1 Infected Subjects
• Actual Study Start Date: Dec 9, 2009
• Actual Primary Completion Date: Nov 25, 2020
• Anticipated Study Completion Date: Oct 31, 2031

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Etravirine Etravirine Dosed by weight up to a maximum dose of 200 milligram (mg) bid until switched to an etravirine (ETR)-based treatment regimens (i.e. commercially available and reimbursed, or accessible through another source) or local standard of care, as appropriate.	Drug: Etravirine; Participants will be dosed with etravirine by weight up to a maximum dose of 200 mg bid until switched to an etravirine-based treatment regimens (i.e. commercially available and reimbursed, or accessible through another source) or local standard of care, as appropriate.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With At-least One Adverse Event as a Measure of Safety Until Etravirine (ETR)-Based Treatment Regimen is Commercially Available [Up to 10 years and 11 months]

   An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participants who meet all of the following criteria are eligible for this trial: Documented HIV-1 infection

• Male or female participants, aged 2 years and older

• Successfully completed a clinical (parent) pediatric trial with ETR sponsored by or in collaboration with Janssen Research & Development, and continues to receive benefit from the use of ETR

• Participant (where appropriate, depending on age) and their parent(s) or legal representative(s) have signed the Informed Consent Form (ICF)/Assent voluntarily

• Children will be informed about the program and asked to give assent (where appropriate, depending on age)

• Negative urine pregnancy test for females of childbearing potential

Exclusion Criteria:

• Participants meeting one or more of the following criteria cannot be selected: Any condition (including but not limited to alcohol and drug use), which in the opinion of the investigator could compromise the participant's safety or adherence to treatment with ETR

• Any active clinically significant disease (e.g., pancreatitis, cardiac dysfunction) or findings of medical history, laboratory or physical examination that, in the investigator's opinion, would compromise the participant's safety during treatment with ETR

• Previously demonstrated clinically significant allergy or hypersensitivity to ETR or to any of the excipients of ETR

• Pregnant or breastfeeding

• Non-vasectomized heterosexually active boys not using safe and effective birth control methods, or not willing to continue practicing these birth control methods, during the trial and until 30 days after the end of the trial (or after the last intake of the investigational medication)

• Girls, who are sexually active and able to become pregnant, not using safe and effective birth control methods, or not willing to continue practicing these birth control methods, during the trial and until 30 days after the end of the trial (or after the last intake of the investigational medication)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Los Angeles	California	United States
2		Washington	District of Columbia	United States
3		New York	New York	United States
4		Philadelphia	Pennsylvania	United States
5		Buenos Aires		Argentina
6		Ciudad Autonoma De Buenos Aire		Argentina
7		Belo Horizonte		Brazil
8		Riberao Preto		Brazil
9		Rio de Janeiro		Brazil
10		Montreal	Quebec	Canada
11		Lyon Cedex 08		France
12		Paris		France
13		Panama City		Panama
14		Rio Piedras		Puerto Rico
15		Bucuresti		Romania
16		Bloemfontein		South Africa
17		Boksburg		South Africa
18		Cape Town		South Africa
19		Dundee		South Africa
20		Durban N/a		South Africa
21		Durban		South Africa
22		George		South Africa
23		Johannesburg		South Africa
24		Newtown		South Africa
25		Pretoria N/a		South Africa
26		Pretoria		South Africa
27		Esplugues De Llobregat		Spain
28		Madrid		Spain
29		Sevilla		Spain
30		Bangkok		Thailand
31		Khon Kaen		Thailand

Sponsors and Collaborators

• Janssen Sciences Ireland UC

Investigators

• Study Director: Janssen Sciences Ireland UC Clinical Trial, Janssen Sciences Ireland UC

Study Documents (Full-Text)

• Study Protocol - Jul 22, 2019
• Statistical Analysis Plan - Jan 20, 2021

More Information

Publications

None provided.

• Responsible Party: Janssen Sciences Ireland UC
• ClinicalTrials.gov Identifier: NCT00980538
• Other Study ID Numbers: CR016408; TMC125-TID35-C239; 2009-013126-16
• First Posted: Sep 21, 2009
• Last Update Posted: Aug 4, 2022
• Last Verified: Aug 1, 2022

• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Janssen Sciences Ireland UC: TMC125-TiDP35-C239; TMC125-C239; TMC125; HIV; Etravirine; Intelence; IntelenceTM
• Additional relevant MeSH terms: HIV Infections; Etravirine

Study Results

Participant Flow

Arm/Group Title	Etravirine
Arm/Group Description	Participants who previously received etravirine (ETR) in clinical trial with ETR (NCT00254046, NCT00255099, NCT00359021, NCT00665847, NCT01504841) sponsored by/in collaboration with Janssen Research & Development and continued to benefit from its use, in countries where ETR was not commercially available, was not reimbursed, and could not be accessed through another source, or where the participant was not eligible for ongoing trials with ETR received ETR 200 milligrams (mg) twice daily (bid) in adults. Pediatric participants received ETR doses as received in previous ETR (parent) trial, with weight based dose adjustment if necessary (ETR 100 mg bid for weight 10 to less than [<] 20 kilograms [kg]; ETR 125 mg bid for weight 20 to <25 kg; ETR 150 mg bid for weight 25 to <30 kg; and 200 mg bid for weight greater than or equal to [>=] 30 kg). Treatment continued until one of the following criteria was met: participant no longer benefited from etravirine treatment, toxicity, loss to follow up, etravirine became commercially available for participants' use.
Period Title: Overall Study
STARTED	180
COMPLETED	0
NOT COMPLETED	180

Baseline Characteristics

Arm/Group Title	Etravirine
Arm/Group Description	Participants who previously received etravirine (ETR) in clinical trial with ETR (NCT00254046, NCT00255099, NCT00359021, NCT00665847, NCT01504841) sponsored by/in collaboration with Janssen Research & Development and continued to benefit from its use, in countries where ETR was not commercially available, was not reimbursed, and could not be accessed through another source, or where the participant was not eligible for ongoing trials with ETR received ETR 200 milligrams (mg) twice daily (bid) in adults. Pediatric participants received ETR doses as received in previous ETR (parent) trial, with weight based dose adjustment if necessary (ETR 100 mg bid for weight 10 to less than [<] 20 kilograms [kg]; ETR 125 mg bid for weight 20 to <25 kg; ETR 150 mg bid for weight 25 to <30 kg; and 200 mg bid for weight greater than or equal to [>=] 30 kg). Treatment continued until one of the following criteria was met: participant no longer benefited from etravirine treatment, toxicity, loss to follow up, etravirine became commercially available for participants' use.
Overall Participants	180
Age (Count of Participants)
<=18 years	71 39.4%
Between 18 and 65 years	106 58.9%
>=65 years	3 1.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.9 (16.92)
Sex: Female, Male (Count of Participants)
Female	112 62.2%
Male	68 37.8%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
ARGENTINA	11 6.1%
BRAZIL	8 4.4%
CANADA	1 0.6%
FRANCE	3 1.7%
ITALY	6 3.3%
PANAMA	4 2.2%
ROMANIA	1 0.6%
SOUTH AFRICA	122 67.8%
SPAIN	7 3.9%
THAILAND	12 6.7%
UNITED STATES	5 2.8%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With At-least One Adverse Event as a Measure of Safety Until Etravirine (ETR)-Based Treatment Regimen is Commercially Available
Description	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Time Frame	Up to 10 years and 11 months

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least one dose of etravirine.

Arm/Group Title	Etravirine
Arm/Group Description	Participants who previously received etravirine (ETR) in clinical trial with ETR (NCT00254046, NCT00255099, NCT00359021, NCT00665847, NCT01504841) sponsored by/in collaboration with Janssen Research & Development and continued to benefit from its use, in countries where ETR was not commercially available, was not reimbursed, and could not be accessed through another source, or where the participant was not eligible for ongoing trials with ETR received ETR 200 milligrams (mg) twice daily (bid) in adults. Pediatric participants received ETR doses as received in previous ETR (parent) trial, with weight based dose adjustment if necessary (ETR 100 mg bid for weight 10 to less than [<] 20 kilograms [kg]; ETR 125 mg bid for weight 20 to <25 kg; ETR 150 mg bid for weight 25 to <30 kg; and 200 mg bid for weight greater than or equal to [>=] 30 kg). Treatment continued until one of the following criteria was met: participant no longer benefited from etravirine treatment, toxicity, loss to follow up, etravirine became commercially available for participants' use.
Measure Participants	180
Count of Participants [Participants]	42 23.3%

Adverse Events

Time Frame	Up to 10 years and 11 months
Adverse Event Reporting Description	Safety analysis set included all participants who received at least one dose of etravirine.
Arm/Group Title	Etravirine
Arm/Group Description	Participants who previously received etravirine (ETR) in clinical trial with ETR (NCT00254046, NCT00255099, NCT00359021, NCT00665847, NCT01504841) sponsored by/in collaboration with Janssen Research & Development and continued to benefit from its use, in countries where ETR was not commercially available, was not reimbursed, and could not be accessed through another source, or where the participant was not eligible for ongoing trials with ETR received ETR 200 milligrams (mg) twice daily (bid) in adults. Pediatric participants received ETR doses as received in previous ETR (parent) trial, with weight based dose adjustment if necessary (ETR 100 mg bid for weight 10 to less than [<] 20 kilograms [kg]; ETR 125 mg bid for weight 20 to <25 kg; ETR 150 mg bid for weight 25 to <30 kg; and 200 mg bid for weight greater than or equal to [>=] 30 kg). Treatment continued until one of the following criteria was met: participant no longer benefited from etravirine treatment, toxicity, loss to follow up, etravirine became commercially available for participants' use.
All Cause Mortality
	Etravirine
	Affected / at Risk (%)	# Events
Total	6/180 (3.3%)
Serious Adverse Events
	Etravirine
	Affected / at Risk (%)	# Events
Total	18/180 (10%)
Cardiac disorders
Myocardial Infarction	1/180 (0.6%)
General disorders
Accidental Death	1/180 (0.6%)
Death	1/180 (0.6%)
Infections and infestations
Chronic Tonsillitis	1/180 (0.6%)
Disseminated Tuberculosis	1/180 (0.6%)
Gastroenteritis	2/180 (1.1%)
Pneumonia	1/180 (0.6%)
Sepsis	1/180 (0.6%)
Injury, poisoning and procedural complications
Brain Herniation	1/180 (0.6%)
Head Injury	1/180 (0.6%)
Limb Injury	1/180 (0.6%)
Radius Fracture	1/180 (0.6%)
Metabolism and nutrition disorders
Hyperglycaemia	1/180 (0.6%)
Hyponatraemia	1/180 (0.6%)
Hypovolaemia	1/180 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant Melanoma	1/180 (0.6%)
Melanoma Recurrent	1/180 (0.6%)
Metastases to Central Nervous System	1/180 (0.6%)
Metastases to Lymph Nodes	1/180 (0.6%)
Nervous system disorders
Encephalopathy	1/180 (0.6%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	1/180 (0.6%)
Psychiatric disorders
Depression	2/180 (1.1%)
Renal and urinary disorders
Acute Kidney Injury	1/180 (0.6%)
Skin and subcutaneous tissue disorders
Angioedema	1/180 (0.6%)
Vascular disorders
Hypovolaemic Shock	1/180 (0.6%)
Other (Not Including Serious) Adverse Events
	Etravirine
	Affected / at Risk (%)	# Events
Total	32/180 (17.8%)
Blood and lymphatic system disorders
Lymphadenopathy	1/180 (0.6%)
Thrombocytopenia	1/180 (0.6%)
Cardiac disorders
Mitral Valve Incompetence	1/180 (0.6%)
Sinus Tachycardia	1/180 (0.6%)
Eye disorders
Conjunctival Haemorrhage	1/180 (0.6%)
Gastrointestinal disorders
Abdominal Pain	1/180 (0.6%)
Abdominal Pain Upper	1/180 (0.6%)
Aphthous Ulcer	1/180 (0.6%)
Diarrhoea	3/180 (1.7%)
Odynophagia	1/180 (0.6%)
Vomiting	1/180 (0.6%)
General disorders
Pyrexia	2/180 (1.1%)
Infections and infestations
Conjunctivitis	1/180 (0.6%)
Gastroenteritis	2/180 (1.1%)
Gastroenteritis Viral	1/180 (0.6%)
Herpes Simplex	1/180 (0.6%)
Influenza	1/180 (0.6%)
Lice Infestation	1/180 (0.6%)
Lower Respiratory Tract Infection	1/180 (0.6%)
Nasopharyngitis	1/180 (0.6%)
Oral Herpes	2/180 (1.1%)
Otitis Media	2/180 (1.1%)
Respiratory Tract Infection	1/180 (0.6%)
Tonsillitis	4/180 (2.2%)
Tracheobronchitis	1/180 (0.6%)
Upper Respiratory Tract Infection	5/180 (2.8%)
Vulvovaginal Candidiasis	2/180 (1.1%)
Injury, poisoning and procedural complications
Ligament Sprain	1/180 (0.6%)
Investigations
Hepatic Enzyme Increased	1/180 (0.6%)
Lipase Increased	1/180 (0.6%)
Musculoskeletal and connective tissue disorders
Back Pain	1/180 (0.6%)
Myalgia	1/180 (0.6%)
Pain in Extremity	1/180 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin Papilloma	1/180 (0.6%)
Nervous system disorders
Headache	2/180 (1.1%)
Neuropathy Peripheral	1/180 (0.6%)
Syncope	1/180 (0.6%)
Pregnancy, puerperium and perinatal conditions
Pregnancy	4/180 (2.2%)
Psychiatric disorders
Anxiety	1/180 (0.6%)
Renal and urinary disorders
Nephropathy	1/180 (0.6%)
Reproductive system and breast disorders
Amenorrhoea	1/180 (0.6%)
Respiratory, thoracic and mediastinal disorders
Cough	5/180 (2.8%)
Nasal Congestion	1/180 (0.6%)
Skin and subcutaneous tissue disorders
Acne	1/180 (0.6%)
Lipoatrophy	1/180 (0.6%)
Lipohypertrophy	1/180 (0.6%)
Neurodermatitis	1/180 (0.6%)
Prurigo	1/180 (0.6%)
Rash	4/180 (2.2%)
Skin Hypopigmentation	1/180 (0.6%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator agrees that before he/she publishes any results of this trial, he/she shall allow at least 45 days for the Sponsor to review the pre-publication manuscript prior to submission of the manuscript to the publisher, as specified in the Clinical Trial Agreement between Institution/Investigator and Sponsor.